Sema-3A indirectly disrupts the regeneration process of goldfish optic nerve after controlled injury

Shira Rosenzweig, Dorit Raz-Prag, Anat Nitzan, Ronit Galron, Ma'Ayan Paz, Gunnar Jeserich, Gera Neufeld, Ari Barzilai, Arieh S. Solomon

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Background: Neurons of adult mammalian CNS are prevented from regenerating injured axons due to formation of a non-permissive environment. The retinal ganglion cells (RGC), which are part of the CNS, share this characteristic. In sharp contrast, the RGC of lower vertebrates, such as fish, are capable of re-growing injured optic nerve axons, and achieve, through a complex multi-factorial process, functional vision after injury. Semaphorin-3A (sema-3A), a member of the class 3 semaphorins known for its repellent and apoptotic activities, has previously been shown to play a key role in the formation of a non-permissive environment after CNS injury in mammalians. Methods: The expression of sema-3A and its effect on regenerative processes in injured gold fish retina and optic nerve were investigated in this study. Unilateral optic nerve axotomy or crush was induced in goldfish. 2 μl sema-3A was injected intraviterally 48 hours post injury. Neuronal viability was measured using the lipophilic neurotracer dye 4-Di-10-Asp. Axonal regeneration was initiated using the anterograde dye dextran. Retinas and optic nerves were collected at intervals of 2, 3, 7, 14 and 28 days after the procedure. Using Western blot and immunohistochemical analysis, the expression levels of semaphorin-3A, axonal regeneration, the removal of myelin debris and macrophage invasion were studied. Results: We found a decrease in sema-3A levels in the retina at an early stage after optic nerve injury, but no change in sema-3A levels in the injured optic nerve. Intravitreal injection of sema-3A to goldfish eye, shortly after optic nerve injury, led to destructive effects on several pathways of the regenerative processes, including the survival of retinal ganglion cells, axonal growth, and clearance of myelin debris from the lesion site by macrophages. Conclusions: Exogenous administration of sema-3A in fish indirectly interferes with the regeneration process of the optic nerve. The findings corroborate our previous findings in mammals, and further validate sema-3A as a key factor in the generation of a non-permissive environment after transection of the optic nerve.

Original languageEnglish
Pages (from-to)1423-1435
Number of pages13
JournalGraefe's Archive for Clinical and Experimental Ophthalmology
Issue number10
StatePublished - Oct 2010


FundersFunder number
EU-STRP BeNatural033256
Israeli Ministry of Health and Lirot
Israeli Research Association for Eye Health and Blindness Prevention
Ministry of Aliyah and Immigrant Absorption


    • Axotomy
    • Injury
    • Optic nerve
    • Regeneration
    • Semaphorin-3A


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